Gamma glutamyl transferase activity in rat colon during experimental colonic carcinogenesis.

Colonic gamma glutamyl transferase activity is raised in colonic malignancy. This study was undertaken to determine how early and how extensively this raised activity occurs during carcinogenesis. Sixty rats were given weekly injections of dimethylhydrazine for 16 weeks, and 20 rats acted as controls. Groups of treated and control rats were sacrificed at regular intervals during the pre-cancerous phase of carcinogenesis, and gamma glutamyl transferase activity was measured at several sites in the colon. Gamma glutamyl transferase activity was raised as early as 4 weeks after the first injection of dimethylhydrazine (p less than 0.05), and the elevation persisted until the development of overt tumours. The raised gamma glutamyl transferase activity was observed throughout both the proximal and distal colon long before the appearance of macroscopic tumours. We conclude that an early and widespread elevation of colonic gamma glutamyl transferase activity occurs during carcinogenesis. This may have useful applications in the early detection of colonic malignancy.

Diagnostic and prognostic problems in early gastric cancer.

Although common in Japan, early gastric cancer is rarely seen in Western countries and generally accounts for only 7 to 10 percent of all gastric malignancies. Eleven patients with early gastric cancer seen over a 10 year period have been reviewed for clinical and pathologic features, method of diagnosis, treatment, and prognosis. The symptoms usually consisted of vague epigastric pain or dyspepsia, but anorexia, weight loss, anemia, and hypoalbuminemia were not commonly seen. Barium meal examination was not helpful in the diagnosis in 50 percent of the patients. The diagnosis was made by endoscopic biopsy of abnormal areas of the stomach, although in 6 of 11 patients, there was no macroscopic suspicion of malignancy. All patients were treated by surgical resection. The tumor was confined to the mucosa in five patients and had infiltrated the submucosa in six patients. The lymph nodes were free of tumor in every patient. At last follow-up, seven patients had survived more than 5 years after operation and were well, although recurrent tumors developed in two patients 3 and 4 years postoperatively but were detected early by endoscopic surveillance. Early gastric cancer has a good prognosis after surgical resection, but the symptoms are vague and the diagnostic tests can be misleading. A vigorous approach to investigation, treatment, and follow-up is necessary to achieve satisfactory results.

Effect of vagal denervation on canine gallbladder motility.

There is an increased incidence of gallstones after truncal vagotomy but the mechanism is unknown. Our aim was to study the early effects of vagotomy on fasting and postprandial gallbladder motility. A chronic model was constructed in 10 dogs to correlate gallbladder motility and emptying with interdigestive and postprandial duodenal motility both before and after selective hepatobiliary vagotomy (five dogs) and truncal vagotomy (5 dogs). During each study recordings were made for one complete interdigestive motor complex (IDMC) and for 90 min after a standard meal of (a) gallbladder and duodenal motility, (b) gallbladder emptying (by a dual radioisotope marker technique) and (c) duodenal output of bilirubin. In control studies the gallbladder contracted at the start of phase II of the interdigestive motor complex and ejected 20-25 per cent of its contents into the duodenum; after meals the gallbladder contracted within 5 min and emptied almost 80 per cent of its contents within 90 min. After both selective hepatobiliary vagotomy and also truncal vagotomy there was no significant difference in the pattern of contraction or emptying of the gallbladder either during fasting or postprandially. We conclude that gallbladder motility and emptying are entirely normal in the early period after vagal denervation.

A scanning electron microscopy study of changes in rat colonic mucosa during carcinogenesis.

Scanning electron microscopy (SEM) has been used to examine morphological changes on the colonic mucosal surface during experimental carcinogenesis. Seventy-five rats were given weekly injections of dimethylhydrazine (DMH) and 25 rats acted as controls. Groups of DMH-treated and control rats were sacrificed at regular intervals and specimens of their colons were examined by SEM. The normal colonic mucosa had an orderly architectural pattern which remained constant throughout the experiment. Abnormalities in the mucosa of treated rats were detected as early as 6 weeks after the first injection of DMH and thereafter there was progressive distortion of the crypts, development of pericryptal fissures and mucosal surface irregularities, and eventually, formation of focal protuberances, polyps, and tumors. The findings indicate that there is a definite pattern of progressive mucosal abnormalities commencing long before the development of focal colon tumors and that SEM is useful in the detection of these abnormalities.

Measurement of high molecular weight forms of enzymes in serum in the detection of hepatic metastases of colorectal cancer.

Total gamma-glutamyl transferase and alkaline phosphatase, liver-specific alkaline phosphatase and high molecular weight forms of the two enzymes were measured in the sera of 42 patients with colorectal cancer, of whom 26 were apparently metastases-free and 16 had palpable liver metastases. The average levels of all enzymes were significantly higher in the group with metastases, but there was considerable overlap between the groups. The predictive values of positive results were of the order of 50-75%; predictive values of negative results were more than 70% for all tests, with high molecular weight alkaline phosphatase (87%) performing best in this respect. However, measurement of high molecular weight enzymes does not offer marked advantages over more conventional enzyme tests in the detection of hepatic metastases of colorectal cancer.

Cryotherapy for advanced haemorrhoids: a prospective evaluation with 2-year follow-up.

The early and long-term results of treating 125 patients with advanced haemorrhoids by cryotherapy have been studied. Hospitalization requirements were brief; 54 per cent of patients were hospitalized for less than 24 h. The only significant early postoperative problem was a profuse serous discharge (67 per cent of patients). Bleeding, pain, or pruritus were rarely encountered. Ninety-three per cent of patients returned to work within 3 weeks. The principal long-term disadvantage was residual peri-anal skin tags and these were excised 6 months postoperatively in 18 patients. Four patients had first or second degree haemorrhoids at 2 years but only one patient (0.8 per cent) had prolapsing piles which required operation. Factors which might have influenced the results have been discussed. It is concluded that cryotherapy is an effective low cost method of dealing with advanced haemorrhoids.

Canine interdigestive and postprandial gallbladder motility and emptying.

The objectives of this study were to characterize intraluminal gallbladder pressure during fasting and postprandially and to determine the relationships between its intraluminal pressure and emptying. Conscious dogs, with chronic indwelling gallbladder and duodenal catheters to measure pressures and infuse nonabsorbable markers, were used to quantify intraluminal pressures and emptying of gallbladder contents and bile into the duodenum during interdigestive and postprandial periods. During the interdigestive period, a brief rise in intragallbladder pressure followed by the flow of bile and 20% of gallbladder marker into the duodenum occurred only during phase II (a period of irregular duodenal contractility preceded by absent duodenal activity, phase I, and followed by a period of regular duodenal contractility, phase III). We suggest that intragallbladder pressure increased secondary to contraction of the gallbladder against a closed sphincter of Oddi and its decline to base line was accompanied by sphincter relaxation, partial gallbladder emptying, and flow of bile into the duodenum. Postprandially, intragallbladder pressure transiently increased and was followed by an isotonic phase lasting 74 +/- 12 min that ended with the onset of rhythmic large-amplitude pressure elevations that continued for 5.1 +/- 1.6 h. Gallbladder emptying was most rapid during the first 30 min postprandially and was completed by 2 h. Thereafter, large-amplitude gallbladder pressure elevations may prevent gallbladder filling and divert hepatic bile into the duodenum until return of the fasting pattern.

A scanning electron microscopy study of changes in the colonic mucus layer during chemical carcinogenesis.

Scanning electron microscopy was used to examine the appearances of the colonic mucus layer of rats during chemical carcinogenesis with dimethylhydrazine. The normal colonic mucus layer had a dense homogeneous appearance and provided a complete cover for the mucosal epithelium. At high magnifications tiny fenestrations could be seen in this mucus layer. During carcinogenesis these fenestrations enlarged, increased in number, and coalesced, causing focal defects in the mucus layer, which eventually broke into strands and clumps of mucus. The findings indicate that the colonic mucus layer develops progressive abnormalities during carcinogenesis which result in breakdown of its integrity and exposure of the mucosal epithelium to colonic contents.

A scanning electron microscopy study of ultrastructural changes in the colonic mucosa of patients with large bowel tumours.

Scanning electron microscopy (SEM) has been used to compare the appearances of the colonic mucosal surface and overlying mucus layer of patients with normal colons, adenomatous polyps and colorectal carcinoma. The normal colonic mucosa had a characteristic orderly arrangement of crypts and was completely covered by an intact mucus layer. Epithelial and cryptal irregularities were seen on the surface of both polyps and carcinomas, and, in addition, the mucus layer was fragmented, leaving areas of the underlying epithelium exposed. These changes were more marked in colorectal cancers than in polyps and were present to a lesser degree in the apparently normal mucosa adjacent to tumours. The findings indicate that SEM can detect minor subtle irregularities on the surface of the colon and so may be useful in detecting pre-neoplastic and early neoplastic changes.

Acute upper gastro-intestinal haemorrhage : A review of 71 cases.

Seventy-one patients with acute upper gastro-intestinal haemorrhage were studied with particular reference to investigations, diagnosis, and history of ingestion of gastro-intestinal irritants. A high incidence of superficial mucosal lesions was found, and the importance of early investigation in the diagnosis of these lesions is stressed. Endoscopy was found to be superior to barium meal in the diagnosis of all sources of haemorrhage except duodenal ulcer. The incidence of multiple lesions was found to be 12.7%, and the value of direct visualisation of bleeding points by endoscopy is emphasised. Almost 16% of the patients underwent urgent surgery, but the mortality rate for the series as a whole was only 2.8%.